A Specific Inhibitor of Cytosolic Phospholipase A2Activity, AACOCF3, Inhibits Glucose-Induced Insulin Secretion from Isolated Rat Islets

In pancreatic β-cells, arachidonic acid accumulation results primarily from phospholipid hydrolysis by phospholipase A2, and activation of this enzyme has been shown to accompany glucose-induced insulin secretion. Inhibitors of phospholipase A2attenuate the secretory response, although the compounds used to date have not discriminated between cytosolic and secretory isoforms of phospholipase A2. In this work, the specific cytosolic phospholipase A2inhibitor, AACOCF3, caused a dose-dependent inhibition of glucose-induced insulin secretion from isolated rat islets and this response was significantly relieved by exogenous arachidonic acid. The results suggest that, despite the low levels of expression of cytosolic phospholipase A2in rat islets, this enzyme contributes to the control of glucose-induced insulin secretion in rat pancreatic β-cells.